MARIO LACOUTURE: How Do I Treat a Patient with Dermatologic Toxicities to EGFR Inhibitors?

Lacouture, Mario E. MD

doi: 10.1097/01.COT.0000399762.77163.85
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Small molecule tyrosine kinase inhibitors and monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) are widely used for a variety of solid tumors. Even though these treatments are tolerated well, dermatological toxicities pose major problems: An acneiform rash affects 70 to 90 percent of patients; dry skin, up to 100%; pruritus, 33%; paronychia, 56%; hair loss, 50%; and hair growth changes, 88%.

Skin being the largest organ in the body, these side effects can affect quality of life significantly. It is important that we learn how to manage these problems well. I will describe here my own approach.

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Acneiform Rash

The papulopustular rash occurs within the first eight weeks in the majority of patients. Based on the results from randomized studies, I use prophylactic minocycline 100 mg once daily or a combined regimen of doxycycline 100 mg bid, hydrocortisone 1% cream to the face and chest, sunscreen, and a moisturizer daily starting from day 1 of therapy, even before rash appears.

I find them to be quite effective in reducing the severity and frequency of Grade $2 skin toxicities by more than 50%.

I continue this regimen daily from day 1 of starting EGFR- directed therapy until the sixth week of therapy. If the rash persists, I will continue for an additional four weeks and then re-evaluate our patients.

I have a low threshold for performing bacterial cultures in areas of rash. I want to point out that in a study of 228 patients treated with EGFR inhibitors, up to 38% of these patients developed infections at sites of skin toxicities. Bacterial infections were the most common, followed by viral and fungal infections. I tend to tailor my antibiotics based on the culture results from these swabs.

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Dry Skin

It has been my experience that nearly everyone will develop dry skin after several months of EGFR- inhibitor therapy. For the face, I use a gentle moisturizer, such as Eucerin cream. For the body, I recommend Aveeno, Cetaphil, or CeraVe creams to be applied within 15 minutes of showering. I advise my patients that skin should be patted dry with a towel before.

For dry skin in the fingertips or heels with thickening and scaling, Ii would recommend an exfoliant such as Lac-Hydrin or Salex cream to the palms and soles.

For fissures in the fingertips, I use Desitin Maximum Strength three times a day. I would also ask my patients to wear cotton socks and gloves at bedtime over the cream.

Since dryness inside the nose usually represents Staphylococcus aureus colonization, I use mupirocin 2% ointment twice daily for two weeks.

As for xerotic dermatitis, (dry skin becoming painful and red) I recommend a topical steroid such as triamcinolone 0.1% cream twice daily. As always in these patients, I would suspect secondary infections in painful areas, especially if there is any yellow crusting or discharge. A bacterial swab culture is recommended to determine culprit and sensitivities.

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Paronychia

Painful paronychia in the fingers or toes occurs in 56% of people treated with EGFR inhibitors. When mild to moderate paronychia develops, I use topical mupirocin 2% ointment and fluocinonide 0.05% bid.

For severe or discharging paronychia with pain, I also recommend soaking fingers or toes in a solution of white vinegar in tap water for 15 minutes every night. Silver nitrate chemical cauterization done weekly is helpful when pain is present.

I usually do it the first time so the patient can see how it is done, and give a prescription so that they can do it at home. For demonstration on how to do this, see this video: http://bit.ly/jG7PWq.

Cultures should be obtained of draining areas for possible secondary infections. Also I recommend soft cotton gloves when performing activities and wearing soft padded shoes and slippers (Tempurpedic slippers, Crocs).

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Itching

Itching is very common, and can occur either on intact skin, or in skin affected by rash or dryness. If the characteristic rash underlies itching, I recommend treating the rash with an oral antibiotic (doxycycline or minocycline 100 mg bid for 4-6 weeks), along with a topical steroid such as triamcinolone 0.1% (Kenalog, Aristocort) or mometasone 0.1% (Elocon) creams twice daily.

Over-the-counter anti-itch creams such as Aveeno Anti-Itch cream or Sarna Ultra Cream are good for the body. For generalized itching that affects quality of life or sleep, systemic antihistamines are useful—I would try a non-sedating antihistamine during the day (Zyrtec, Allegra) and Benadryl or Atarax in the evening (this could also help with sleep).

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Topical Steroids

For topic steroids for the face, I recommend hydrocortisone 2.5% (Hytone) or alclometasone 0.5% (Aclovate) cream twice daily for up to eight weeks. After that, a reevaluation of the severity of rash is recommended to determine continued therapy.

For the body, triamcinolone 0.1% (Kenalog, Aristocort) or mometasone 0.1% (Elocon) creams twice daily, also for up to eight weeks.

And for the scalp, use Clobex solution or shampoo since hair-bearing areas are not amenable to treatment with creams or ointments.

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Comments, Questions?

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© 2011 Lippincott Williams & Wilkins, Inc.
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